| 摘要: |
| ［摘要］目的 探讨辛伐他汀联用HRZ（异烟肼+利福平+吡嗪酰胺三联抗结核药）导致肝损害的特征．方法 8周龄SD大鼠54只，随机分为3组：A组（空白对照组）、B组（HRZ组）、C组（辛伐他汀联合HRZ组），每组18只，雌雄各半，予相应药物灌胃，于10 d、20 d、40 d各组分别处死6只，取肝组织制作HE染色病理切片，处死前股动脉放血检测肝功能．结果 C组总胆红素、直接胆红素全程高于A组，差异有统计学意义，P＜0.05，且给药10 d显著高于20 d和40 d，差异有统计学意义（P＜0.05），呈迅速下降趋势； C组谷丙转氨酶随着给药时间延长呈升高趋势，至给药40 d，组内、组间比较差异有统计学意义，P＜0.05；给药时间延长至40 d，C组肝索排列紊乱、肝细胞肿胀、泡性脂肪变、细胞核浓缩、染色质凝聚、炎细胞浸润等病理改变．结论 辛伐他汀联合HRZ，早期即出现明显胆汁淤积；随着给药时间延长，胆汁淤积程度下降，谷丙转氨酶反而呈升高趋势，且肝组织出现细胞肿胀、泡性脂肪变、细胞核浓缩、染色质凝聚、炎细胞浸润等病理改变． |
| 关键词: ［关键词］辛伐他汀 抗结核药 药物性肝损伤 动脉硬化 联合用药 |
| DOI： |
| 分类号: |
| 基金项目:［基金项目］昆明市卫生局科研基金资助项目（2012-01） |
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| Characteristic of Liver Injury Induced by Simvastatin Combined with HRZ in SD Rats |
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LI Sheng-hao1,2
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1.（1）Cardiology Department;2）Pharmacy Department，The Third People’s Hospital of Kunming，Kunming Yunnan 650041，China）
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| Abstract: |
| ［Abstract］Objective To study the characteristics of liver injury induced by simvastatin combined with HRZ （ Isoniazid， Rifampicin and Pyrazinamide ） in SD rats. Methods Fifty-four 8-week-old SD rats were randomly divided into 3 groups: group A（ control ）， group B （ HRZ ） and group C （ simvastatin combined to HRZ ）， half of each group were male. We calculated the accurate dose respectively before those rats were given intragastrical administration of corresponding drugs. Six rats were killed in each group on 10th ， 20th and 40th day， respectively. Before this， blood was fastened from femoral of every rat that would be killed to test liver function， liver tissue slices were made in order to observe the pathological characteristic. Results Alanine amiotransferase of group C elevated in line with time and reached statistic difference on 40th day， furthermore， it was significantly higher than group A（ P＜0.05）. Total bilirubin and direct Bilirubin of group C were significantly higher than those of group A from the beginning to the end（P＜0.05）， however， they declined rapidly on 10th day， this trend also had statistic difference（P＜0.05）. At the end of this experiment， hepatic cords was disordered slightly，but swelling liver cells and vacuolar degeneration were observed， the nuleus of cell condensed. Soakage of monocytes， neutrophils， and lymphocytes occurred in the portal and lobule regions，or even spotty necrosis occasionally. Conclusion Cholestasis occurs at the early stage when simvastatin is combined with HRZ in SD rats，however，it has a rapidly degressive trend. In contrast，Alanine amiotransferase elevates，furthermore，pathological injury or even spotty necrosis can emerge in liver tissue slices. |
| Key words: ［Key words］Simvastatin Anti-tuberculosis drug Drug induced liver injury Arteriosclerosis Combined drugs |